Yin-Xi Zhang

Background: Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis presents relapse risk and potential functional impairment, with no established maintenance treatment guidelines. Objectives: The study aimed to uncover prognostic signatures, and identify predictors of relapse and poor outcome using real-world evidence. Design: This multicenter retrospective study included anti-LGI1 encephalitis patients from five tertiary hospitals in Eastern China between January 2015 and January 2024, with ≥ 24-month follow-up. Methods: Relapse was defined as the presence of new or worsening clinical features after at least 3 months of stability or improvement. Poor outcome was defined as a modified Rankin Scale score > 2 at last follow-up. Results: A total of 104 patients were included (median age 56.5 years, 60.6% male). Following the acute phase, the majority (66.3%) received prolonged corticosteroid treatment (≥6 months) without steroid-sparing maintenance immunotherapy (SSMI), whereas 16.3% received SSMI. Twelve patients (11.5%) experienced relapse. Hyponatremia at diagnosis was more common in relapsing patients ( p = 0.017), and was significantly associated with an increased risk of relapse in Cox regression (hazard ratio = 4.67, 95% confidence interval [CI] = 1.41–15.53, p = 0.012). Poor outcome was observed in 17 patients (16.3%), with male sex (odds ratio [OR] = 5.12, 95% CI = 1.27–34.48, p = 0.041) and hyponatremia (OR = 4.69, 95% CI = 1.54–15.47, p = 0.008) as potential risk factors. Conclusion: This study suggests that hyponatremia is associated with an increased risk of relapse and poor outcome in anti-LGI1 encephalitis. These findings may facilitate individualized risk stratification, but further validation in larger prospective cohorts is needed.

Background The 2024 McDonald criteria for multiple sclerosis (MS) introduced novel biomarkers (central vein sign, paramagnetic rim lesion, kappa free light chain) alongside conventional updates. However, access to these novel markers is regionally limited, making the conventional components the most feasible option in many clinical settings. Yet real-world evidence on their diagnostic performance remains limited, prompting this evaluation in Chinese patients with suspected MS. Methods We retrospectively enrolled 184 patients aged 12–50 years with a first central nervous system demyelinating event or atypical presentation with MS-suspicious imaging, and lesions in ≥ 2 of 5 anatomical regions. Diagnostic assessments were performed per the 2017 and 2024 criteria. Results The 2024 criteria identified 173 patients (94.0%) versus 166 (90.2%) by the 2017 criteria (p = 0.023), with substantial concordance (κ = 0.739). The 2024 criteria yielded seven additional diagnoses, including two with 4–5 regions without the need for dissemination in time (DIT), three fulfilling dissemination in space (DIS) via the optic nerve as the fifth region, and two atypical presentation cases diagnosed by DIS plus DIT. The 2024 criteria significantly reduced required clinical attacks (p = 0.037). While median diagnostic time did not differ significantly (p = 0.058), five patients achieved markedly earlier diagnosis (median advance 47 months). Subgroup analysis showed a higher diagnostic rate in patients with a single clinical attack (p = 0.041). Conclusion Even without novel biomarkers, the conventional components of the 2024 criteria improved sensitivity in high-lesion burden or atypical cases—a conservative estimate supporting real-world clinical use in China.

Anti-IgLON5 disease is a rare neuronal surface antibody-associated encephalopathy characterized by complex and diverse clinical manifestations, including sleep disturbances, bulbar symptoms, abnormal movements, cognitive decline, and occasionally, neuropsychiatric abnormalities. Immunotherapy is a mainstay of treatment. However, most patients still experience poor outcomes. We report the case of a 72-year-old female who presented with intractable insomnia and progressive mutism. Upon further evaluation, anti-IgLON5 antibodies were detected in both serum and cerebrospinal fluid via cell-based assay, leading to the final diagnosis of anti-IgLON5 disease. The patient failed to improve with intravenous immunoglobulin at the outside hospital; similarly, high-dose intravenous methylprednisolone at our institution yielded no clear benefit. Subsequently, efgartigimod, a neonatal Fc receptor inhibitor, was incorporated into the treatment regimen, resulting in significant clinical improvement, as evidenced by substantial reductions in both the modified Rankin Scale score and anti-IgLON5 disease composite score. To our knowledge, this is the first case report on efgartigimod for treating anti-IgLON5 disease. As an adjuvant therapy, efgartigimod demonstrated promising efficacy, suggesting its potential as a treatment option, especially in patients with limited response to conventional immunotherapy.

Purpose: Autoimmune limbic encephalitis (ALE) often occurs with detectable neuronal antibodies, presenting with seizures as a prominent clinical manifestation. We aimed to investigate the clinical characteristics and seizure outcomes in a cohort with antibody-positive ALE. Methods: We consecutively recruited patients with antibody-positive ALE and new-onset seizures between July 2014 and February 2024. Their demographic, clinical, and paraclinical characteristics, and treatment were collected. Seizure outcomes during follow-up were evaluated respectively, as well as the associated risk factors. Results: Seventy-two patients were included, and the associated autoantibodies targeted the leucine-rich glioma-inactivated 1 (LGI1), gamma-aminobutyric acid type B receptor (GABA_BR), and glutamic acid decarboxylase 65 (GAD65). Secondarily generalized tonic-clonic seizures and focal non-motor seizures were the most prevalent seizure semiologies, and 28 (38.9%) patients exhibited multiple seizure types. Furthermore, among 54 patients with over two years of follow-up, 16 (29.6%) experienced intermittent seizures lasting for more than one year. Younger onset, specific antibodies, and multiple seizure types were correlated with the longer seizure duration (all P < 0.05). Six (11.1%) patients continued to have seizures even after two years of follow-up, comprising two with LGI1 and four with GAD65 antibodies. Female sex, younger onset, and specific antibody profiles were significantly associated with sustained seizures, indicating autoimmune-associated epilepsy (AAE, all P < 0.05). Conclusion: In patients with antibody-positive ALE, seizure outcomes appeared to change over an extended follow-up period, particularly in those with LGI1 and GABA_BR antibodies. Younger age at disease onset, female sex, and specific antibody profiles may be indicators of AAE.

In dipeptidyl-peptidase-like protein 6 (DPPX) antibody-associated encephalitis, DPPX antibodies from serum and CSF target the extracellular subunit of the voltage-gated potassium channel 4.2. This targeting leads to a characteristic clinical triad comprising gastrointestinal symptoms (predominantly diarrhea), cognitive-psychiatric dysfunction, and manifestations of CNS hyperexcitability, with hyperekplexia being a more specific feature. This rare disease typically presents with a subacute or chronic course and often affects middle-aged and older individuals. Patients may have a weak association with certain hematologic malignancies, particularly lymphoma and chronic lymphocytic leukemia. Brain MRI typically shows normal findings or nonspecific white matter changes. DPPX antibody-associated encephalitis responds well to immunotherapy, and most patients ultimately present with a good prognosis. However, relapses can occur. To improve our understanding of this rare but treatable autoimmune encephalitis and avoid misdiagnosis, we conduct a systematic review and summarize the current knowledge of its clinical and paraclinical features, management, and prognosis.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a newly described rare entity of drug-resistant epilepsy, with a wide spectrum of presentations. We aim to describe the diagnostic features and prognosis of MOGHE in a large cohort. We performed a systematic review preregistered on PROSPERO (CRD42023472978), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Embase, Scopus, and ScienceDirect between database inception and November 30, 2023, for all published studies on MOGHE. Inclusion criteria were a histopathologic diagnosis of MOGHE. The risk of bias was analyzed with a standardized tool specifically for case reports and case series. The demographic, clinical, EEG, neuroimaging, genetic, and neuropathologic features; treatments; and prognosis were extracted and analyzed. Subgroup analysis was performed with the age at onset and SLC35A2 variant status. A total of 163 patients with MOGHE from 18 studies were included in the analysis. The median age at seizure onset was 1.2 years, and 103 were male. Ninety-five patients presented with unilobed lesions. Ninety-nine had lesions in the frontal lobe. A total of 101 patients achieved a favorable surgical outcome. Patients with an onset before 10 years were more likely to present with epileptic spasms, the West syndrome, a circumscribed pattern of interictal EEG, intellectual disabilities, and a better seizure outcome, compared with those with an onset age 10 years and older. Forty-five patients (72.6%) were SLC35A2-positive. Patients harboring the SLC35A2 variants were more likely to present as Lennox-Gastaut syndrome, when compared with those who were SLC35A2-negative. MOGHE is a distinct entity of drug-resistant epilepsy associated with SLC35A2 variants, characterized by age-dependent phenotypes. The study emphasizes the clinical pearls indicative of the rare disease, which may facilitate early recognition and appropriate selection of treatments. The included studies were case reports or series, which were mainly limited by selection and reporting biases.

Background Neuronal surface antibody-associated autoimmune encephalitis (NSAE) is a group of neuro-inflammatory disorders that is mediated by autoantibodies against the cell-surface and synaptic antigens. Studies have explored the role of neurofilament light chain (NfL) in NSAE and provided inconsistent data. We performed a systematic review and meta-analysis to evaluate the NfL levels in the serum and cerebrospinal fluid (CSF) of patients with NSAE. Methods The National Center for Biotechnology Information (NCBI, PubMed), Web of Knowledge, and the Cochrane Library databases were searched for studies reporting NfL levels in patients with NSAE. Random-effects meta-analysis was used to pool results across studies. Results Thirteen studies were included in the final systematic review and meta-analysis. The serum NfL levels were significantly higher in patients with NSAE compared to unaffected controls (standardized mean difference [SMD] = 0.909, 95% confidence interval [CI]: 0.536–1.282). Similarly, the CSF NfL levels were elevated in patients with NSAE (SMD = 0.897, 95% CI: 0.508–1.286). The serum and CSF NfL levels were not significantly correlated with disease severity, prognosis, and abnormalities in magnetic resonance imaging, electroencephalography, and CSF. Conclusions NfL levels in the serum and CSF were higher in patients with NSAE compared to unaffected controls. However, the NfL levels were not shown to be significantly associated with clinical or paraclinical features.

The clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have been found to overlap with several other diseases. The new criteria proposed in 2023 were designed to better identify the disease but require validation across various populations to ascertain its clinical utility. We aimed to investigate the diagnostic performance in phenotypically diverse patients. This multicenter study retrospectively included adult and pediatric patients who were hospitalized for a first suspected demyelinating event and tested positive for MOG immunoglobulin G (IgG) during the acute phase. The 2023 Lancet Neurology criteria were assessed against the benchmark of empirical clinical diagnosis, and the 2018 JAMA Neurology and Journal of Neuroinflammation criteria were also evaluated for comparative analysis. Among the 291 eligible patients (82 adults, 209 children), 282 (96.9%) were clinically diagnosed as definite MOGAD (77 adults, 205 children), while 262 (90.0%) fulfilled the 2023 diagnostic criteria (78 adults, 184 children). A total of 265 patients met the criteria for core clinical demyelinating events, and 76 (26.1%) had serum clear positive MOG-IgG (≥ 1:100). The sensitivity of the 2023 criteria was 0.91 (adults vs. children = 0.97 vs. 0.89), the specificity was 0.56 (adults vs. children = 0.40 vs. 0.75), positive likelihood ratio was 2.06 (adults vs. children = 1.62 vs. 3.57), and negative likelihood ratio (NLR) was 0.15 (adults vs. children = 0.06 vs. 0.14). Additionally, 264 and 256 cases were classified as definite MOGAD by the 2018 JAMA Neurology and Journal of Neuroinflammation criteria, respectively. Compared to the 2023 diagnostic criteria, the 2018 JAMA Neurology criteria demonstrated similar diagnostic performance. However, the 2018 Journal of Neuroinflammation criteria exhibited comparable sensitivity (0.92, adults vs. children = 0.96 vs. 0.89), higher specificity (1.00, adults vs. children = 1.00 vs. 1.00) and better NLR (0.09, adults vs. children = 0.04 vs. 0.11). The 2023 criteria demonstrated good sensitivity in adult and pediatric patients in China yet modest specificity. Close follow-up is needed for patients with atypical phenotypes but high-titer MOG-IgG to avoid underdiagnosis.

Herpes simplex virus-2 encephalitis (HSV2E) in immunocompetent adults is exceptionally rare, and the subsequent onset of autoimmune encephalitis after HSV2E is even less common. This report presents the inaugural Chinese case of anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) induced by HSV2E, confirmed via metagenomic next-generation sequencing (mNGS). The patient demonstrated a favorable response to intravenous immunoglobulin (IVIG) monotherapy. This case emphasizes the importance of considering autoimmune encephalitis in patients exhibiting new or recurrent neurological symptoms after HSV2E recovery. Comprehensive mNGS and neuronal antibody testing are essential for timely diagnosis. Moreover, IVIG monotherapy can serve as an effective treatment for NMDARE induced by HSV2, providing a viable alternative, particularly when steroid therapy is contraindicated.

Cerebellar ataxia is an uncommon and atypical manifestation of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, often accompanied by seizures, psychiatric symptoms, and cognitive deficits. Previous cases of isolated brainstem-cerebellar symptoms in patients with anti-NMDAR encephalitis have not been documented. This report presents a case of anti-NMDAR encephalitis in which the patient exhibited cerebellar ataxia, nystagmus, diplopia, positive bilateral pathological signs, and hemiparesthesia with no other accompanying symptoms or signs. The presence of positive CSF anti-NMDAR antibodies further supports the diagnosis. Other autoantibodies were excluded through the use of cell-based assays. Immunotherapy was subsequently administered, leading to a gradual recovery of the patient.